168 Chapter 5 leptin than normal adipocytes.42 Therefore rise in leptin could be a result of leptin resistance and not fat accumulation. It would be interesting to evaluate fat mass and leptin longitudinally and in a standardized way during multiple dexamethasone courses to gain better understanding in the interplay between both. Despite the fact that we observed a significant rise in leptin levels and hunger scores after five days of dexamethasone, we could not establish the expected association between both. This may be due to the fact that parents reported the feeling of hunger for their child and it was not always possible to ask the children to participate in these questions because of their young age. Validated questionnaires that measure feeling of hunger or eating behavior are scarce, not available in every language and often only parent-reported or as self-report commence from the age of seven or higher.8,43 Thus, measuring the feeling of hunger in young children remains challenging and this may have influenced our results. Still, previous research showed a dexamethasone-induced increase in food intake, including increased total protein, fat, saturated fat, carbohydrate, as well as sodium intake, after four days of dexamethasone treatment.8 This undesirable increase in quantitative and qualitative food intake may be a direct effect of dexamethasone, independent of leptin signaling. Parents reported that fatigue and sleep problems increased during the dexamethasone course, as was previously reported by us and others.5,44-47 In the general population, sleep deprivation is known to decrease leptin levels and to increase hunger and appetite.17 In our cohort, we did not find an association between the change in leptin values and sleep problems, nor between changes in sleep problems and hunger scores. Interestingly, previous studies showed that, when measuring sleep objectively with actigraphy, sleep duration increased during dexamethasone administration.45,46 Furthermore, one study in healthy children (n = 37) showed that increased sleep duration was associated with decreased leptin values.48 In our cohort, 60% of the parents indicated that their child slept the same or more during dexamethasone, but this was not associated with the change in leptin values. However, we based our results on a single item of the SDSC questionnaire, which is a meagre substitute for true sleep duration. There are no studies in children linking fatigue and leptin. Leptin has been linked to pathological inflammatory fatigue in adults, possibly through the release of proinflammatory cytokines.49-52 Dexamethasone suppresses inflammatory responses and may therefore moderate the association between fatigue and leptin in our cohort. In addition, it is conceivable that in children with ALL, other factors such as chemotherapy, immobilization and hospital visits may influence sleep, fatigue and leptin values independently, influencing possible associations between the changes that occur during dexamethasone.
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